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Objectives Cognitive impairment caused by cerebrovascular disease accounts for more than half of vascular dementia. However, neuropsychological tests are limited by their subjectivity. Additional effective approaches to evaluate cognitive impairment in patients with cerebrovascular disease are necessary. Method One hundred and thirty-two patients with cerebrovascular disease were recruited. One hundred participants met the criteria and completed neuropsychological scales. Sixty-nine participants proceeded with polysomnography, and 63 of them had their peripheral blood biomarkers measured. According to Mini-Mental State Examination scores, patients were divided into cognitively impaired and cognitively normal groups. The differences in biomarkers and sleep parameters between the groups were compared, and decision tree models were constructed to evaluate the evaluation ability of these indicators on cognitive decline. Results The integrated decision tree model of sleep parameters yielded an area under curve (AUC) of 0.952 (95% confidence interval [CI]: 0.911–0.993), while that of plasma biomarkers yielded an AUC of 0.872 (95% CI: 0.810–0.935) in the assessment of cognition status. Then the participants were automatically clustered into mild and severe cognitive impairment groups by multiple neuropsychological test results. The integrated plasma biomarker model showed an AUC of 0.928 (95% CI: 0.88–0.977), and the integrated sleep parameter model showed an AUC of 0.851 (95% CI: 0.783–0.919) in the assessment of mild/severe cognitive impairment. Discussion Integrated models which consist of sleep parameters and plasma biomarkers can accurately evaluate dementia status and cognitive impairment in patients with cerebral small vessel disease. This innovative study may facilitate drug development, early screening, clinical diagnosis, and prognosis evaluation of the disease.

Abstract: Alzheimer's disease (AD) is an intricate neurodegenerative disease with chronic and progressive development whose typical neuropathological features encompass senile plaques and neurofibrillary tangles, respectively formed by the extracellular deposition of amyloid-beta (Aβ) and the intracellular accumulation of hyperphosphorylated tau protein in the brain, particularly in limbic and cortical regions. The pathological changes are considered to be caused by the loss of Aβ and tau protein clearance mechanisms under pathological conditions, which leads to an imbalance between the rates of clearance and production. Consequently, the main strategies for treating AD aim to reduce the production of Aβ and hyperphosphorylated tau protein in the brain, inhibit their accumulation, or accelerate their clearance. Although drugs utilizing these therapeutic strategies have been studied successively, their therapeutic effects have generally been less than ideal. Fortunately, recent advances have been made in clearance strategies for these abnormally expressed proteins, including immunotherapies and nanomedicines targeting Aβ or tau, which could represent an important breakthrough for treating AD. Here, we review recent development of the strategies for the removal of abnormal proteins and provide new ideas and methods for treating AD.

The South Qiangtang terrane (SQT), the Tibetan representative of the Cimmerian continent, is bounded in the south by the Bangong-Nujiang suture zone (BNSZ). The BNSZ is geologically manifested by the Mugagangri Group (MG) accretionary complexes developed during northward Meso-Tethyan subduction, whose timing and processes are, however, contentious. Herein, we conducted provenance analysis on the MG trench deposits, via petrography, whole-rock geochemistry and detrital-zircon geochronology. The results reveal a complete picture of provenance evolution during passive- to active-margin transition (from subduction initiation through fringing oceanic-arc, to continental-arc developments) at the SQT margin. In particular, the earliest trench deposits (subunit Trma; ~222 Ma), which contain olistostromes with blocks of oolitic limestone shed from the destructing SQT passive margin, mark the subduction initiation. A second subunit (Trmb; ~210 Ma) has periodically elevated volcanogenic components. Conglomerates of subunit Trmb have abundant basaltic clasts of intra-oceanic arc geochemical affinities, which were likely derived from an intra-oceanic arc fringing the SQT. The youngest subunit (Jmd; ~190 Ma) exhibits enriched ferromagnesian elements and a major youngest detrital-zircon age peak, indicating a continental-arc provenance. Moreover, detrital-zircon age spectra suggest that, at ~210 Ma, the central Qiangtang metamorphic belt became an important source area, and the North Qiangtang terrane (NQT) replaced SQT as the main provenance. This is best explained by that the SQT underthrusted beneath the NQT and was downwarped to form a foreland basin. Our findings confirm that the initial subduction of Meso-Tethys beneath SQT was coeval to other Cimmerian terranes, likely a uniform response to the Paleo-Tethys closure and collision between Eurasia (NQT) and Cimmeria (SQT).

In many industry applications, the self-locking and interlocking switches are usually used to control electrical equipment or applied to automation control. The electronic self-locking /interlocking switches can improve the disadvantages of the conventional self-locking/interlocking switches using relay types; however, they can not achieve the real interlocking state when two push buttons are pressed at the same time. In this paper, a fully self-locking/interlocking electronic switch circuit based on MOSFET is proposed to solve the above problem by using a technology of signal mutual control.